Pathway of Alzheimer’s degeneration discovered

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Scientists at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University have used a unique approach to track brain degeneration in Alzheimer’s disease, uncovering a pathway through which degeneration spreads from one region to another.

Individuals in the early stages of Alzheimer’s disease (AD) were scanned using both structural magnetic resonance imaging (sMRI) and positron emission tomography (PET). The scientists were interested in how AD affects the basal forebrain – a deep brain structure that supplies the outer cortex with acetylcholine, a neurotransmitter that is critical for maintaining normal brain function. They found that as cholinergic neurons in the basal forebrain degenerate, the areas in the cortex which receive their cholinergic inputs also degenerate.

Based on post-mortem examinations of brain tissue, it has been known for quite some time that the cholinergic neurons are particularly vulnerable to degeneration in Alzheimer’s disease. However, this study is among the first in which scientists were able to track degeneration of cholinergic neurons in living humans. “A key finding from this study is that the results from sMRI scans matched what we were seeing on PET scans, despite the fact they provide different types of measurements and were performed on different patients” said Dr. Nathan Spreng, Director of the Laboratory of Brain and Cognition at The Neuro. “The combination of PET with sMRI may therefore represent be a powerful tool for tracking the progression of Alzheimer’s disease in living patients.”

“This study shows PET and sMRI scans could potentially be used to diagnose Alzheimer’s disease before cognitive symptoms appear, giving doctors a better window of time to work on prevention,” said Taylor Schmitz, researcher in Dr. Spreng’s lab and the study’s lead author. “Drugs that promote the delivery of acetylcholine to these cortical regions could be one way to prevent degeneration.”

The results of this study were published in the journal Cell Reports on July 3, 2018. Schmitz says that he would like to follow up with a larger study of patients in earlier stages of the disease, and perform structural MRI and PET on the same patients to confirm the previous study’s results.

The study was supported in part by a grant from the Canada First Research Excellence Fund and the National Institute on Aging.

The Neuro

The Montreal Neurological Institute and Hospital – The Neuro – is a world-leading destination for brain research and advanced patient care. Since its founding in 1934 by renowned neurosurgeon Dr. Wilder Penfield, The Neuro has grown to be the largest specialized neuroscience research and clinical center in Canada, and one of the largest in the world. The seamless integration of research, patient care, and training of the world’s top minds make The Neuro uniquely positioned to have a significant impact on the understanding and treatment of nervous system disorders. The Montreal Neurological Institute is a McGill University research and teaching institute. The Montreal Neurological Hospital is part of the Neuroscience Mission of the McGill University Health Centre. For more information, please visit www.theneuro.ca